Transdermal delivery of medicinal agents provides advantages over other routes of administration. For example, first-pass metabolism and variable rates of absorption associated with oral administration of medicinal agents can be avoided by transdermal administration. Intravenous injection and other methods of administering a medicinal agent by injection can cause pain upon insertion of a hypodermic needle into the patient. Transdermal administration can avoid pain at the site of administration and provide the further advantage that a medicinal agent can be administered continuously over several days without any continued action by the patient.
Multiple parties have investigated transdermal delivery of contraceptive agents to control fertility. See, for example, U.S. Pat. Nos. 5,296,230; 5,512,292; and 5,788,983. Advantages of transdermal delivery of contraceptive agents include improved patient compliance when using a multi-day, easy-to-use patch and reduced occurrence of over-dosing or under-dosing of the contraceptive agent, as can sometimes occur when patients are tasked with repeated oral administration of a contraceptive agent.
Transdermal delivery systems containing estrogens and/or progestins have been described. See, for example, U.S. Pat. Nos. 5,296,230; 5,512,292; and 5,788,983. One challenge for achieving effective contraception by transdermal delivery of an estrogen and/or progestin is the low skin permeability of many estrogens and/or progestins. Certain penetration enhancers have been described for increasing the rate at which certain medicinal agents permeate the skin. For example, U.S. Pat. No. 7,045,145 describes a combination of skin penetration enhancing agents that include dimethyl sulfoxide. However, transdermal formulations containing dimethyl sulfoxide suffer from various disadvantages, including malpleasant odors and potential complications during manufacturing of the transdermal delivery system due to the volatility of dimethyl sulfoxide. Further, the use of skin penetration enhancers in the transdermal delivery device can cause undesirable side effects, such as irritation of the patient's skin depending on the concentration and identity of agents used to increase skin penetration of the medicinal agent.
Therefore, the need exists for new transdermal delivery systems and methods for transdermally administering a medicinal agent. The present invention addresses this need and provides other related advantages due in part to the discovery of a novel combination of agents that increase the skin penetration rate of contraceptive agents levonorgestrel and ethinyl estradiol.